Elimination of Onchocerciasis from Mexico

Background

Mexico is one of the six countries formerly endemic for onchocerciasis in Latin America. Transmission has been interrupted in the three endemic foci of that country and mass drug distribution has ceased. Three years after mass drug distribution ended, post-treatment surveillance (PTS) surveys were undertaken which employed entomological indicators to check for transmission recrudescence.

Methodology/Principal findings

In-depth entomologic assessments were performed in 18 communities in the three endemic foci of Mexico. None of the 108,212 Simulium ochraceum s.l. collected from the three foci were found to contain parasite DNA when tested by polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA), resulting in a maximum upper bound of the 95% confidence interval (95%-ULCI) of the infective rate in the vectors of 0.035/2,000 flies examined. This is an order of magnitude below the threshold of a 95%-ULCI of less than one infective fly per 2,000 flies tested, the current entomological criterion for interruption of transmission developed by the international community. The point estimate of seasonal transmission potential (STP) was zero, and the upper bound of the 95% confidence interval for the STP ranged from 1.2 to 1.7 L₃/person/season in the different foci. This value is below all previous estimates for the minimum transmission potential required to maintain the parasite population.

Conclusions/Significance

The results from the in-depth entomological post treatment surveillance surveys strongly suggest that transmission has not resumed in the three foci of Mexico during the three years since the last distribution of ivermectin occurred; it was concluded that transmission remains undetectable without intervention, and Onchocerca volvulus has been eliminated from Mexico.     

Comparison of techniques for the measurement of skin temperature during exercise in a hot,humid environment

Exercising or working in a hot, humid environment can results in the onset of heat-related illness when an individual''s temperature is not carefully monitored. The purpose of the present study was to compare three techniques (data loggers, thermal imaging, and wired electrodes) for the measurement of peripheral (bicep) and central (abdominal) skin temperature. Young men and women (N = 30) were recruited to complete the present study. The three skin temperature measurements were made at 0 and every 10-min during 40-min (60% VO₂max) of cycling in a hot (39±2°C), humid (45±5% RH) environment. Data was statistically analyzed using the Bland-Altman method and correlation analysis. For abdominal skin temperature, the Bland-Altman limits of agreement indicated that data loggers (1.5) were a better index of wired than was thermal imaging (3.5), For the bicep skin temperature the limits of agreement was similar between data loggers (1.9) and thermal (1.9), suggesting the both were suitable measurements. We also found that when skin temperature exceeded 35°C, we observed progressively better prediction between data loggers, thermal imaging, and wired skin sensors. This report describes the potential for the use of data loggers and thermal imaging to be used as alternative measures of skin temperature in exercising, human subjects.     

Investigating hydrophobic ligand–receptor interactions in parathyroid hormone receptor using peptide probes

With an increasing number of new chemical entities entering clinical studies, and an increasing share of the market, peptides and peptidomimetics constitute one of the most promising classes of therapeutics. The success of synthetic peptides as therapeutics relies on the lead optimization step in which the lead candidates are modified to improve drug‐like properties of peptides related to potency, pharmacokinetics, solubility, and stability, among others. Peptidomimetics based on the N‐terminal stretch of the first 11 amino acids of the PTH have been investigated as potential lead compounds for the treatment of osteoporosis. On the basis of a peptide reported in the literature, referred to here as the Parent Peptide (H‐Aib‐Val‐Aib‐Glu‐Ile‐Gln‐Leu‐Nle‐His‐Gln‐Har‐NH₂), we conducted systematic SAR analyses to investigate the effects of altering peptide hydrophobicity on PTH receptor functional potency as measured by the cAMP (cyclic adenosine monophosphate) accumulation and β‐arrestin recruitment assays. Among hydrophobic residues, we found that the Val2 position shows the least flexibility in terms of the SAR studies, whereas the Leu7 position appeared to be most flexible. Through circular dichroism and nuclear magnetic resonance spectroscopy studies, we were able to establish that changes in hydrophobic residues significantly change the extent of peptide helicity and that the helical character correlates well with receptor agonist activity. Here, we report several novel PTH 1–11 peptidomimetics that show comparable or enhanced potency to stimulate G_s‐signaling over β‐arrestin recruitment as compared with such properties of PTH 1–34 and the Parent Peptide. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.     

Soil‐nutrient availability under a global‐change scenario in a Mediterranean mountain ecosystem

Changes in rainfall availability will alter soil‐nutrient availability under a climate‐change scenario. However, studies have usually analyzed the effect of either drier or wetter soil conditions, despite the fact that both possibilities will coexist in many climatic regions of the world. Furthermore, its effect may vary across the different habitats of the ecosystem. We experimentally investigated the effect of three contrasting climatic scenarios on different carbon (C), nitrogen (N), and phosphorus (P) fractions in soil and microbial compartments among three characteristic habitats in a Mediterranean‐type ecosystem: forest, shrubland, and open areas. The climatic scenarios were dry summers, according to the 30% summer rainfall reduction projected in the Mediterranean; wet summer, simulating summer storms to reach the maximum historical records in the study area; and current climatic conditions (control). Sampling was replicated during two seasons (spring and summer) and 2 years. The climatic scenario did not affect the nutrient content in the litter layer. However, soil and microbial nutrients varied among seasons, habitats, and climatic scenarios. Soil‐nutrient fractions increased with lower soil‐moisture conditions (dry scenario and summer), whereas microbial nutrients increased under the wet summer scenario and spring. This pattern was consistent both studied years, although it was modulated by habitat, differences being lower with denser plant cover. Holm oak seedlings, used as live control of the experiment, tended to increase their N and P content (although not significantly) with water availability. Thus, the results support the idea that higher rainfall boosts microbial and plant‐nutrient uptake, and hence nutrient cycling. By contrast, a rainfall reduction leads to an accumulation of nutrients in the soil, increasing the risk of nutrient loss by leaching or erosion. These results show that the projected climate change will have significant effects on nutrient cycles, and therefore will have important implications on the ecosystem functioning.     

Effects of age,territoriality and breeding on survival of Bonelli’s Eagle Aquila fasciata

Survival typically contributes most to population trends in long‐lived birds and its accurate estimation is therefore vital for population management and conservation. We evaluated the effects of age, territoriality and reproduction on survival in Bonelli’s Eagle Aquila fasciata through multistate capture‐mark‐recapture analyses on a long‐term dataset. Monitoring was carried out in southeast France (1990–2008) and involved the surveying of territorial Eagles, the marking of fledged chicks, and the recording of resightings and recoveries of marked non‐territorial and territorial birds. Survival improved with age, but territoriality was not retained in the best model; yearly survival was estimated at 0.479 for fledglings (to 1 year of age), 0.570 for 1‐ and 2‐year‐olds, and 0.870 for 3‐year‐old and older individuals. The second best model supported a further increase in survival from 3‐year‐olds (0.821) to older individuals (0.880). In the third best supported model, territoriality enhanced survival, but only in 2‐year‐olds (0.632 vs. 0.562 for non‐territorial). We found no correlation between the previous breeding stage and future survival, consistent with the long lifespan of the study species. Nevertheless, 4‐year‐old and older successful breeders were more likely to breed the following year than failed adult breeders (0.869 vs. 0.582), suggesting that the cost of reproduction is small in comparison with the variation in quality among individuals or their territories.     

Pannexin-1 is required for ATP release during apoptosis but not for inflammasome activation

Apoptotic cell death is important for embryonic development, immune cell homeostasis, and pathogen elimination. Innate immune cells also undergo a very rapid form of cell death termed pyroptosis after activating the protease caspase-1. The hemichannel pannexin-1 has been implicated in both processes. In this study, we describe the characterization of pannexin-1-deficient mice. LPS-primed bone marrow-derived macrophages lacking pannexin-1 activated caspase-1 and secreted its substrates IL-1β and IL-18 normally after stimulation with ATP, nigericin, alum, silica, flagellin, or cytoplasmic DNA, indicating that pannexin-1 is dispensable for assembly of caspase-1-activating inflammasome complexes. Instead, thymocytes lacking pannexin-1, but not the P2X7R purinergic receptor, were defective in their uptake of the nucleic acid dye YO-PRO-1 during early apoptosis. Cell death was not delayed but, unlike their wild-type counterparts, Panx1(-/-) thymocytes failed to recruit wild-type peritoneal macrophages in a Transwell migration assay. These data are consistent with pannexin-1 liberating ATP and other yet to be defined "find me" signals necessary for macrophage recruitment to apoptotic cells.     

A new Late Jurassic turtle from Spain: phylogenetic implications,taphonomy and palaeoecology

Abstract: The Jurassic was an important period in the evolution of Testudinata and encompasses the origin of many clades, and this is especially true of Jurassic turtles from Western Europe. A new genus and species of Late Jurassic turtle, Hispaniachelys prebetica gen. et sp. nov. from the upper Oxfordian of the Prebetic (Southern Spain), is described on the basis of postcranial material. The specimen is the only known tetrapod from the Mesozoic of the Prebetic and the oldest turtle from southern Europe. A mosaic of characters indicates this is a new genus: it displays basal features including dorsal epiplastral processes/reduced cleithra, no medial contact of the extragulars and a long first thoracic rib, alongside derived characters including an absence of mesoplastra and the vertebral 3/4 sulcus crossing neural 5. The phylogenetic position of the new taxon is hard to resolve, and it might be either a paracryptodire or a basal testudine, but it is distinct from Plesiochelys. A complex taphonomic history is shown by a range of overlying grazing traces and bioerosion on the carapace. The carapace was subsequently overturned and buried ventrally up, terminating grazing activity, and was then bored by sponges before final burial. Scanning electron microscopy reveals phosphatic microspheroids associated with bacterial decay in the vascular cavities of the cancellous bone, suggesting the carapace may have acted as a closed microenvironment in which decay‐derived authigenic minerals formed.     

The balance of proangiogenic and antiangiogenic VEGFA isoforms regulate follicle development

Vascular endothelial growth factor A (VEGFA) has been extensively studied because of its role in follicular development and is a principal angiogenic factor essential for angiogenesis. Since vascularization of the theca layer increases as follicles progress in size through preantral and antral stages, VEGFA might influence follicle growth via the regulation of angiogenesis. However, VEGFA might also influence follicular development through nonangiogenic mechanisms, since its expression has been localized in nonvascular follicles and cells. Alternative mRNA splicing of eight exons from the VEGFA gene results in the formation of various VEGFA isoforms. Each isoform has unique properties and is identified by the number of amino acids within the mature protein. Proangiogenic isoforms (VEGFA_XXX) are encoded by exon 8a, whereas a sister set of isoforms (VEGFA_XXXB) with antiangiogenic properties is encoded by exon 8b. The antiangiogenic VEGFA_XXXB isoforms comprise the majority of VEGFA expressed in most tissues, whereas expression of the proangiogenic VEGFA isoforms is upregulated in tissues undergoing active angiogenesis. Although proangiogenic and antiangiogenic isoforms can now be distinguished from one another, many studies evaluating VEGFA in ovarian and follicular development up to now have not differentiated proangiogenic VEGFA from antiangiogenic VEGFA. Experiments from our laboratory indicate that proangiogenic VEGFA promotes follicle recruitment and early follicular development and antiangiogenic VEGFA inhibits these processes. The balance of proangiogenic versus antiangiognic VEGFA isoforms is thus of importance during follicle development. Further studies are warranted to elucidate the way that this balance regulates follicular formation and progression.